Progressive MS – Masitinib another duck lines up at MSVirtual2020


There is further hope in the horizon for progressive MS. The Phase III clinical trials were announced at MS Virtual 2020 this Sunday, adding a second third agent to the potential hopefuls in the progressive MS armamentarium. The first two being ocrelizumab and siponimod.

Masitinib is designed to block the activity of multiple cell types, including microglia/macrophages, neutrophils, mast cells and Schwann cells. In MS, it is being developed to treat progressive MS. And from the looks of the clinical trial results, masitinib may just do this. It met its primary endpoint reducing disability progression on EDSS up to week 96 (p=0.0256, see below); it reduced the risk of first disability progression by 42% (p=0.0342) and the risk of 3 month disability progression by 37% (although this was not significant statistically).

So, it would seem drugs targeting innate immunity (microglia/macrophages, mast cells etc) may work in progressive disease. More therapies targeting these cell types may therefore just be the way to go!

FC04.01 – Masitinib in primary progressive (PPMS) and non-active secondary progressive (nSPMS) multiple sclerosis: Results from phase 3 study AB07002



Masitinib (MAS) is a small molecule drug targeting KIT, LYN and CSF1R. Proof-of-concept that MAS slows progressive multiple sclerosis (MS) was previously demonstrated.


Assessment of oral MAS as a treatment for progressive MS. Study AB07002 (NCT01433497) evaluated 2 independent parallel groups; 4.5 mg/kg/d vs matched placebo (PBO), and titrated MAS dose of 6.0 mg/kg/d vs PBO.


Randomized (2:1), double-blinded, placebo-controlled, 2-parallel group trial. Eligible patients (pts) aged 18­–75 years, with baseline Expanded Disability Status Scale (EDSS) 2.0–6.0, regardless of time-from-onset, and diagnosed with primary progressive (PPMS) or non-active secondary progressive (nSPMS) MS, were treated for 96 weeks. Primary endpoint was overall EDSS change from baseline using repeated measures (GEE model, timeframe W12–W96, measured every 12 weeks). Results are expressed as least-squares means difference (δEDSS, positive value indicates worsening), with treatment-effect reported as between-group difference (ΔLSM, negative value favors MAS). A key sensitivity analysis was the 3-level ordinal EDSS model (±1 or 0, repeated measures), which simultaneously measures improved, stable, or worsening outcomes over duration of treatment.


MAS (4.5mg/kg/d) (n=199, median EDSS=5.5, mean age=49.3±9.6 years) showed significant benefit over PBO (n=101) with δEDSS of 0.001 vs 0.098, respectively, and ΔLSM of -0.097(95%CI[-0.192,-0.002]);p=0.0256. This treatment-effect was numerically maintained for the subgroups of nSPMS (MAS n=120 vs 56) and PPMS (MAS n=79 vs 45) with ΔLSM of -0.104(95%CI[-0.198,-0.008]; p=0.032) and -0.128(95%CI [-0.285,0.0282];p=0.108), respectively. All EDSS sensitivity analyses were convergent with the primary outcome, including the conservative jump-to-reference approach with ΔLSM of -0.089 (95%CI[-0.173,-0.006];p=0.0367). Ordinal EDSS analysis showed a significant 39% relative probability of either reduction in EDSS progression or increase in EDSS improvement (hazard ratio (HR) 0.610 (95%CI[0.376,0.988];p=0·0446). Analysis of EDSS time-to-progression showed a significant reduced relative risk of 42% with MAS for first progression (HR 0.58, 95%CI[0.35,0.96];p=0.034), and a reduced relative risk of 37% with MAS for 12-week confirmed (HR 0.63, 95%CI[0.33,1.20];p=0.159). The proportion of pts presenting at least one adverse event (AE) was 94.5% for MAS (4.5 mg/kg/d) vs 87.1% for PBO. Safety was consistent with the known profile for MAS, common treatment-emergent AEs being diarrhea, nausea, rash, and hematological assessments. Efficacy results from the MAS high-dose parallel group (titrated 6.0 mg/kg/d) were inconclusive and no new safety signal was observed.


MAS (4.5 mg/kg/d), a first-in-class TKI targeting the innate immune system via inhibition of mast cell and microglia/macrophage activity, may provide a new treatment option for PPMS and nSPMS

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Neuro Doc Gnanapavan


  • Wonderful news! Do I understand correctly an another two year phase III study is required to get MAS approved as a medicine for MS?

  • I am not a native speaker. But what do you mean with another duck? You think, this medicine will not work? If yes, why do you think that, since the trials data looks promising?

    Have you heard some words on the future timeline?
    Also I read elsewhere, they want to do another confirmation study. But I could not find out, why? Do you know, which aspects make another confirmation study necessary, since I understood, their last study was already a phase 3 study.
    Thank you

    • Hi Christine, Ducks in line (row) referring to getting a task complete in reference to anti-inflammatory agents that have been shown to work in progression MS.

      The trial data is definitely promising, AB Science currently own the drug and I suspect a big pharma May purchase the drug, but AB pharma has said that they would be starting a second confirmatory study.

  • Doesn’t a 37% reduction in disability tells you it only affects part of ms progression pathway. The actual MS pathology is still not understood or discovered? If it was then it should stop ms in its tracts. Inspite of therapeutic lag. Especially in younger patients who will have their repair processes kick in. Unfortunately this not promising enough.

    • Let’s just say progression is one third inflammation, one third neuronal/axonal health, one third regenerative capacity in concept – this gives you a fair idea on what is needed in terms of treatments.

      • Okay. Let’s go along with this, so this drug then affects the inflammation part. But say if you are young, and disease duration is less than 5 years. Then this implies for those people on this drug would mean a complete stop in ms right? As there isn’t time enough to cause damage to repair and axional health. Was this observed in the trial?

  • Ok, so to over simplify matters, how does a promising TKI go against our best anti CD 20 indication for progressive MS? I’m assuming thus will boil down to a one vs the other and not an add-on option.



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